Using four transplantable mouse colon tumor lines, chemically induced in our laboratories, we have biologically characterized those tumors and determined their responsiveness to clinically used chemotherapeutic agents. (Five additional mouse colon tumors have now been chemically induced and established in serial transplantation.) Since one or more of these tumors, ranging in morphologic grade and metastatic potential, respond to the major classes of chemotherapeutic agents effective in man, we propose to use these tumor lines as potential predictive models for human colorectal cancer. Primary emphasis will be placed on their use in the selection of new chemotherapeutic agents. Specifically, we will attempt to identify (from agents reported to demonstrate activity in other tumor systems or to have structures or mechanisms of peculiar interest) active single agents and their optimal dose/schedule relationships. New active agents thus selected will be evaluated in combination with other known active agents for evidence of potentiation and determination of optimal dose-timing relationships. In addition, active single agents and combinations will be evaluated for possible use as adjuvants to other treatment modalities, primarily - but not restricted to - primary tumor excision. Finally, these tumor lines will continue to be used in the development of concepts and principles of chemotherapy in an attempt to answer important and basic clinical questions.